Heart attack is a leading cause of death. Until recently it was thought that the oxygen deprivation to the heart muscle, cardiac ischemia, was the significant cause of damage to the heart in heart attack victims. While true that lack of oxygen to the heart or a region of the heart will eventually result in cell death, no significant injury occurs to the heart for at least thirty to forty minutes in the absence of molecular oxygen. Recent findings suggest that the much of the injury to the heart following an ischemic event of relatively short duration occurs during the reperfusion of the ischemic tissue with oxygenated blood and may be caused by oxygen derived free radicals.
The compound 1,3-dihydro-4-methyl-5-[4-(methyl-thio)benzoyl-2H-imidazol-2-one, enoximone, and the compound 1,3-dihydro-4-ethyl-5-(4-pyridinylcarbonyl)-2H-imidazol-2-one, piroximone, are known from U.S. Pat. Nos. 4,405,635 and 4,405,628, respectively, to be cardiotonic agents useful in the treatment of heart failure, for example, congestive heart failure. Enoximone and piroximone apparently function by increasing cardiac contractility thereby increasing the pumping ability of the heart. The stronger heart is then better able to supply blood to the organs of the body. While perhaps not curing or treating the underlying condition or disease causing the heart failure, enoximone and piroximone treat the most serious symptom, i.e. lack of adequate blood supply to the tissues and organs of the body. Enoximone and piroximone may also act to relieve the symptoms of heart failure by acting as vasodilators, thereby reducing the resistance of the flow of blood to the body tissues.
1,3-dihydro-4-methyl-5-[4-(methylthio)benzoyl-2H-imidazol-2-thione, the thio analog of enoximone, and 1,3-dihydro-4-ethyl-5-(4-pyridinylcarbonyl)-2H-imidazol-2-thione, the thio analog of piroximone, the compounds of this invention, are also generically known from U.S. Pat. No. 4,405,628 and are also generically disclosed there to be cardiotonic agents. Indeed applicants have determined that the thio analog of enoximone has about one-tenth the potency of enoximone and the thio analog of piroximone about one-eighteenth the potency of piroximone in enhancing cardiac contractile stength. Now it has been discovered that the thio analog of enoximone, 1,3-dihydro-4-methyl-5-[4-(methylthio)benzoyl]-2H-imidazol-2-thione, and the thio analog of piroximone, 1,3-dihydro-4-ethyl-5-(4-pyridinylcarbonyl)-2H-imidazol-2-thione, as well as certain of their derivatives when administered to a patient prior to an ischemic event, during an ischemic event, or during the period of time subsequent to an ischemic event during which reperfusion damage occurs, prevents or lessens the damage which normally occurs when circulation is restored to the portion of the heart deprived of blood.